Obiettivo It is now widely accepted that tumors are composed of heterogeneous population of cells, which contributeto many aspects of treatment resistance observed in clinic. Despite the acknowledgment of the tumor cellheterogeneity, little evidence was shown about complexity and dynamics of this heterogeneity in vivo,mainly because of lacking flexible genetic tools which allow sophisticated analysis in primary tumors. Werecently developed a very efficient mouse somatic brain tumor model which have a full penetrance of highgrade glioma development. Combination of this model with several transgenic mouse lines allow us toisolate and track different population of cells in primary tumors, most importantly, we also confirmed thatthis can be done on single cell level. Here I propose to use this set of valuable genetic tools to dissect thecellular heterogeneity in mouse gliomas. First we will perform several single cell lineage tracing experimentto demonstrate the contribution of brain tumor stem cell, tumor progenitors as well as the relativelydifferentiated cells, which will provide a complete data sets of clonal dynamics of different tumor cell types.Second we will further perform this tracing experiment with the presence of conventional chemotherapy.Third we will perform single cell RNA sequencing experiment to capture the molecular signature, whichdetermines the cellular heterogeneity, discovered by single cell tracing. This result will be further validatedby analysis of this molecular signatures in human primary tumors. We will also use our established in vivotarget validation approach to manipulate the candidate molecular regulators to establish the functionalcorrelation between molecular signature and phenotypic heterogeneity. This project will greatly improve ourunderstanding of tumor heterogeneity, and possibly provide novel approaches and strategies of targetinghuman glioblastomas. Campo scientifico medical and health sciencesmedical biotechnologygenetic engineeringnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsRNA Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-CoG-2014 - ERC Consolidator Grant Invito a presentare proposte ERC-2014-CoG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-COG - Consolidator Grant Istituzione ospitante DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG Contribution nette de l'UE € 2 000 000,00 Indirizzo IM NEUENHEIMER FELD 280 69120 Heidelberg Germania Mostra sulla mappa Regione Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 000 000,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG Germania Contribution nette de l'UE € 2 000 000,00 Indirizzo IM NEUENHEIMER FELD 280 69120 Heidelberg Mostra sulla mappa Regione Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 000 000,00
